Note: The risk of bias by domain corresponds to the highest risk of bias among outcomes by domain.
The overall risk of bias corresponds to the overall highest risk of bias assessed among outcomes.
Bias | Author's judgement | Support for judgement |
Randomization |
Low |
Quote: “The randomization schedule was generated by the contract manufacturing organization and incorporated into the labeling of kits. MDI kits were sent to the study sites in blocks of 6 with 3 active and 3 placebo kits randomized within each block. Individual site personnel dispensed individual kits in order, blinded to the assignment.”
Comment: Allocation sequence random. Allocation sequence probably concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
Deviations from intervention |
Low |
Quote: “Double blind”
Comment: Blinded study (participants and personnel/carers) Our analysis for the binary outcomes is an intention-to-treat analysis. This method was considered appropriate to estimate the effect of assignment to intervention. Risk assessed to be low for the outcomes: Mortality (D28). Mortality (D60 or more). Hospitalization or death. Adverse events. Serious adverse events. |
Missing outcome data |
Some concerns |
Comment: 400 participants randomized; 400 participants analyzed.
Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons: 11 vs 9 were lost to follow up, 5 vs 4 withdrawal by patient, 2 vs 7 had an AE with hospitalization, 1 vs 1 had an AE without hospitalization and 0 vs 1 discontinued at the physician discretion. Missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome (similar reasons and proportions of missingness between arms). Risk assessed to be some concerns for the outcomes: Mortality (D28). Mortality (D60 or more). Hospitalization or death. Adverse events. Serious adverse events. |
Measurement of the outcome |
Low |
Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups. Blinded study (outcome assessor). Risk assessed to be low for the outcomes: Mortality (D28). Mortality (D60 or more). Hospitalization or death. Adverse events. Serious adverse events. |
Selection of the reported results |
Low |
Comment: The protocol, statistical analysis plan, and registry were available (consulted up to version dated May 19th, 2020).
Outcomes pre-specified. Results were not selected from multiple outcome measurements or analyses of the data. Trial analyzed as pre-specified. Risk assessed to be low for the outcomes: Mortality (D28). Mortality (D60 or more). Hospitalization or death. Adverse events. Serious adverse events. |
Overall risk of bias |
Some concerns |